Prevalence of germline BRCA1/2 pathogenic variants in unselected Korean patients with HER2-negative metastatic breast cancer: a nationwide prospective study (KCSG BR19-10)
Year: 2025
Type: article
Study design: Observational Study
Abstract: Background Assessment of germline (g) BRCA1/2 status is recommended for all patients with HER2-negative metastatic breast cancer (MBC) to identify candidates for poly(ADP-ribose) polymerase (PARP) inhibitor therapy, which is not always possible in clinical practice due to limited testing resources. In this study, we investigate the cross-sectional prevalence of g BRCA1/2 pathogenic variant (PV) carriers in unselected Korean patients with HER2-negative MBC. Methods Patients diagnosed with HER2-negative metastatic BC receiving palliative systemic treatment were eligible for inclusion in the study. Peripheral blood was prospectively drawn from each patient and g BRCA1/2 status was assessed by next-generation sequencing using an NGeneBio BRCAaccuTest. Findings A total of 586 patients were enrolled between October 2019 and March 2022, and the prevalence of g BRCA1/2 PV was analyzed in 570 patients. The median age at enrollment was 54 years (interquartile range, 48–61) and 567 patients were female. Among the 570 patients with g BRCA1/2 analysis, 481 had hormone receptor–positive/HER2-negative breast cancer (BC) and 89 had triple-negative breast cancer (TNBC). The overall prevalence of g BRCA1/2 PV carriers was 7.4% (42/570, 95% confidence interval (CI) 5.4%–9.8%) in unselected patients with HER2-negative MBC [g BRCA1 , 1.8% (95% CI 0.8%–3.2%), 10/570; g BRCA2 , 5.6%(95% CI % - 7.8%), 32/570]. The overall prevalence of g BRCA1/2 PV carriers in Korean patients with HER2-negative MBC and a low risk of hereditary breast ovarian cancer syndrome (HBOC) was 5.7% [19/332, 95% confidence interval 3.5%–8.8%; TNBC 10.5% (95% CI 1.3%–33.1%), 2/19; HR-positive/HER2-negative 5.4%(95% CI 3.2%–8.6%), 17/313]. Interpretation Our study measured the size of the current underestimation of g BRCA1/2 PV carriers in unselected Korean patients with HER2-negative MBC, particularly in patients without high risk factors for HBOC. An active screening strategy for unselected HER2-negative MBC should be pursued to avoid missing potential candidates for systemic treatment with PARP inhibitors. Funding Pfizer.
Authors: Hee Kyung Ahn, Jee Hung Kim, Su-Jin Koh, Joohyuk Sohn, Myoung Joo Kang, Kyung Hae Jung, Kyoung Eun Lee, Jieun Lee, Sung Ae Koh, Yee Soo Chae, Jae Ho Byun, In Hae Park, Hee-Jun Kim, Jee Hyun Kim, Han Jo Kim, Joo Young Jung, Jung Lim Lee, Yoon Young Cho, Kyong Hwa Park, Ji-Yeon Kim, Seock-Ah Im, Yeon Hee Park
Institutions: Samsung Medical Center, Sungkyunkwan University, Seoul National University, Yonsei University, Seoul National University Bundang Hospital, Gangnam Severance Hospital, University of Ulsan, Ulsan University Hospital, Yeungnam University College, Yeungnam University, Yonsei Cancer Hospital, Inje University, Inje University Haeundae Paik Hospital, Asan Medical Center, Ewha Womans University, Daegu Fatima Hospital, The Catholic University of Korea Seoul St. Mary's Hospital, Catholic University of Korea, Kyungpook National University Chilgok Hospital, The Catholic University of Korea Incheon St. Mary's Hospital, Korea University, Korea University Guro Hospital, Soonchunhyang University, Soonchunhyang University Hospital Cheonan, Chung-Ang University Healthcare System, Chung-Ang University, Hallym University, Hallym University Medical Center, Daegu Catholic University Medical Center, Korea University Anam Hospital, Seoul National University Hospital
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $4,250
Award: G8523661457
OpenAlex ID: W4412048736